Dilemmas in Elderly Diabetes and Clinical Practice Involving Traditional Chinese Medicine

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development.


Introduction
According to the 10th edition of the International Diabetes Federation's Diabetes Atlas (https://diabetesatlas.org/atlas/tenth-edition/, accessed on 1 May 2024), approximately 536.6 million individuals worldwide were afflicted with diabetes in 2021, constituting 10.5% of the global population.By 2045, the prevalence is projected to reach 12.2%, encompassing 783.2 million individuals [1].Global expenditure on diabetes-related health has notably increased, increasing from USD 232 billion in 2007 to USD 966 billion in 2021, among adult patients, signifying a 316% increase over a 15-year time span.China, as a populous nation, has a substantial diabetes burden, affecting not only its general populace, but also its elderly population.According to data from China's seventh national population census, the incidence of elderly individuals with DM (≥60 years) increased significantly to 30%, impacting 260 million people in 2020 [2,3].An estimated 45% to 47% of older adults are prediabetic [3,4].
The elderly population is at increased risk of diabetes, making it a key demographic for diabetes prevention and management [5,6].Elderly individuals with diabetes often experience asymptomatic hyperglycemia, worsened metabolic dysregulation, occult microvascular and macrovascular complications, and heightened susceptibility to acute adverse events [7].Given the diverse pathophysiological factors associated with aging, the management strategies for elderly patients with diabetes differ significantly from those for younger individuals.The existence of conflicting treatment options in relation to elderly patients with diabetes exacerbates the challenges faced in treatment.Furthermore, insufficient attention is currently being devoted to addressing the unique needs of elderly individuals with diabetes [8,9].It is imperative to prioritize a comprehensive approach that integrates individualized care, effectiveness, and safety.
For millennia, traditional Chinese medicine (TCM) has been utilized in China, demonstrating efficacy in alleviating symptoms and enhancing quality of life, with notable treatment adherence and safety [10,11].TCM offers a distinctive perspective on the etiology and progression of conditions such as diabetes and aging, including imbalances in Yin and Yang, disruptions in the flow of Qi and Xue, and the dysfunction of ZangFu, which symbolize the internal organs and their respective functions [12].For instance, Qi-tonifying herbs could promote energy metabolism to control weight and boost immunity against diabetic complications.Moreover, fundamental research has been undertaken to investigate the systematic anti-diabetes and anti-aging mechanisms of TCM formulas, medicinal herbs, and active natural products at cellular and molecular levels [13][14][15].Clinical trials involving elderly individuals with diabetes and common diabetic complications have demonstrated the benefits of TCM in terms of three-level prevention, exercise guidance, symptom management, weight, nutrition, and complication management [15].To the best of our knowledge, this study represents the first attempt to compile a comprehensive review of the challenges faced by elderly individuals with diabetes and to summarize the clinical evidence pertaining to TCM and relevant natural products.The primary objective of this investigation is to present a critical analysis of the clinical application of TCM and natural products in the management of diabetes among the elderly population, encompassing the present status, clinical considerations, existing TCM strategies, and future perspectives in this field.

Lack of Timely Diagnosis and Inadequate Prevention of Diabetes in Elderly People
Increasing age is one of the risk factors for diabetes [6].For elderly people with diabetes risk factors, the purpose of prevention is to intervene in abnormal glucose tolerance, reduce the rate of diabetes, reduce the incidence of complications, reduce the incidence of adverse reactions and mortality, and improve the quality of life [9].Given the elevated incidence of diabetes among elderly individuals, recommendations have been made for early prevention, diagnosis, and treatment [5].Nevertheless, the current strategies for preventing diabetes in elderly people are inadequate, with a prevailing trend toward ineffectiveness and pessimism [5,9].Due to the presence of atypical symptoms and numerous complications, the rate of diagnosis and treatment for elderly individuals with diabetes is regrettably low.Additionally, elderly patients with diabetes who present with acute and complex symptoms are prone to misdiagnosis and underdiagnosis.For the secondary prevention of diabetes, we have summarized related potential preclinical and clinical interventions in a previous review [16].The crosstalk network between metabolic disorders, immuno-inflammation, and endothelial dysfunction may provide novel and effective therapeutic targets for DVC prevention, while TCM and natural product interventions, such as rhein, hirudin, and polysaccharides, still deserve further study because they have unique advantages for DVC prevention.The primary prevention of diabetes may be a more pressing emergency that we should effectively address.Thus, we further reviewed publications of meta-analyses and systematic reviews that shed new light on the primary prevention of DM (Tables 1 and S1).Cognitive decline in individuals with diabetes was highlighted, with a reduced ability to live independently, reduced compliance, reduced effects of lifestyle interventions, and offsets in terms of the endeavor toward diabetes education and the prevention of diabetes [26].The mechanisms include neuroinflammation as a result of chronic inflammation in elderly people with diabetes, which increases the risk of central degenerative diseases and psychiatric disorders [27,28].A systematic review of 17 studies, involving 1.7 million patients, revealed that people with diabetes had an approximately 2.25-fold greater risk of developing Alzheimer's disease than the people without diabetes [29].The treatment of cognitive impairment in elderly patients with diabetes poses a significant challenge due to a lack of early identification of risk factors, such as hypoglycemia [30].Addressing issues such as poor compliance, public health education, and health promotion is crucial in managing this population.It is imperative for elderly people to engage in and assimilate into society to mitigate and postpone cognitive decline [31].The elderly population demonstrates a low health education acceptance rate, and further research from government and society is needed to address the societal impact and policy implementation related to elderly diabetes [32][33][34].It is essential to advocate for the prevention and rehabilitation of DM in elderly people, with the involvement of family members to cater to the diverse needs of elderly individuals.Extensive evidence from experimental data has illustrated that TCM is effective in the treatment of diabetic cognitive decline, with few adverse effects [35,36].Evidence-based TCM interventions for diabetic cognitive decline are relatively insufficient (Tables 2 and S2).

Nutritional Imbalances and Restricted Dietary Intake in Elderly Patients with Diabetes
Achieving a balanced diet and proper nutrition is a desired outcome, while overnutrition issues such as being overweight, obesity, and inadequate nutrition-induced frailty and sarcopenia significantly impact elderly patients with diabetes [41,42].Over 50% of elderly individuals with diabetes are diagnosed with obesity or as being overweight, and data from the Beijing Longitudinal Study of Aging II (BLSA-II) indicate a high prevalence (19.32%) and incidence (12.32%) of frailty in this population [43,44].A review of epidemiological studies in Asian countries, using the AWGS 2014 standard, revealed that the prevalence of sarcopenia ranged from 5.5% to 25.7% [45].
On the one hand, restricted dietary intake helps individuals lose weight, control blood glucose, and even exert anti-aging effects [46][47][48][49].On the other hand, adequate nutrition is a necessary guarantee to prevent and control adverse consequences related to malnutrition in elderly individuals [50].However, a diet that is too heavy or restricted may not be appropriate for the elderly population.It is advisable that elderly individuals enhance their nutritional and protein consumption to maintain healthy dietary practices, avoid overly restrictive energy intake, prioritize a well-rounded diet with balanced nutrition, favor carbohydrates with a low glycemic index, ensure adequate intake of high-quality protein, be vigilant of malnutrition in elderly individuals with diabetes, routinely utilize nutritional risk screening tools for assessing nutritional risk, and aim for the prompt detection of risk factors and interventions to enhance patient outcomes [5,51].To achieve and maintain a healthy weight, it is important to approach weight loss in a methodical manner that includes a balance of fat loss and muscle gain.This necessitates a thorough examination of weight loss, dietary interventions, and protein intake in elderly patients with diabetes.Sarcopenia is intricately linked to the aging process, as elderly individuals experience alterations in organ function and hormone levels that contribute to diminished exercise capacity, skeletal muscle mass, muscle strength, and overall physical function [52].Older diabetes patients exhibit an extended disease duration, characterized by heightened levels of advanced glycation end products and reactive oxygen species, resulting in a reduction in capillary density, type II muscle fibers, and impaired muscle synthesis within the muscle tissue [53].Insulin resistance in elderly individuals with diabetes mellitus hastens the onset of sarcopenia [54].Malnutrition, which leads to decreased muscle protein synthesis, serves as a significant etiological factor and robust indicator for the progression of sarcopenia.Dietary interventions in isolation often fail to supply sufficient nutrients for elderly patients with sarcopenia, necessitating the potential consideration of oral supplementation.Furthermore, the consumption of proteins rich in essential amino acids is typically advised [55].However, individuals with diabetic nephropathy may face unique considerations in this context.The dietary guidelines for individuals with diabetes and kidney disease suggest a focus on consuming high-quality protein, while limiting the intake of plant-based proteins [56].It is important to be cautious of potential adverse reactions in the gastrointestinal tract when using anti-diabetes medications, such as glucagon-like peptide-1 receptor agonists, as they may lead to malnutrition, sarcopenia, and frailty [57][58][59].Part 4 of this study delves into further precautions and adverse effects associated with anti-diabetes medications.For TCM interventions, acupuncture has been proposed as a potential treatment for obesity and diabetes, and a few high-quality clinical meta-analyses and systemic reviews have reported on the use of TCM and natural products for treating obesity, frailty, and sarcopenia in elderly populations [60][61][62][63].The systemic reviews and meta-analyses on TCM and natural products for the treatment of obesity, frailty, and sarcopenia are shown in Tables 3 and S3.

Sports Health and Safety Are Equally Important for Elderly People with Diabetes
The dilemma involving sports health and safety for elderly people with diabetes is also a problem that needs to be solved.Falls are common adverse events for older adults.According to WHO statistics (https://www.who.int/publications/i/item/9789241563536, accessed on 1 May 2024; https://www.who.int/news-room/fact-sheets/detail/falls,accessed on 1 May 2024), the incidence of falls in elderly individuals aged 65 years and above is 28~35% worldwide, and for those aged 70 years and above, it is as high as 32~42%.Each year, an estimated 684,000 individuals die from falls globally; thus, falls and related injuries are serious obstacles to healthy aging.Older individuals need to engage in consistent and moderate physical activity, select activities that align with their physical capabilities and health status, and incorporate balance and flexibility exercises into their routine.Prioritizing the safety of exercise for elderly individuals is crucial for preventing the worsening of health conditions, resulting from falls and prolonged bed rest.TCM fitness training, which includes Tai Chi, Ba Duan Jin, and Wu Qin Xi, has been demonstrated to be beneficial for promoting physical stability and decreasing the likelihood of falls [93,94].Thus, we reviewed the systemic reviews and meta-analyses on TCM exercise for the treatment of diabetes and related complications in elderly individuals (Table 4).

Medication Safety in Blood Glucose Management for Elderly People with Diabetes
Diverse anti-diabetes medications exert blood glucose regulatory effects through different mechanisms.For various comorbid diseases and special conditions in the elderly population, diabetes control regimens become more complex, and medication application becomes tricky.Anti-diabetic therapeutic regimens that avoid the risk of hypoglycemia and underweight people, allow elderly patients with diabetes to adjust individualized medication plans, while ensuring medication safety [115].
TCM also has significant advantages in decreasing blood glucose with medication.In addition to TCM exercise, an increasing number of TCM prescriptions play a good alternative role, some of which even have high-quality clinical evidence (Table 5).Although the anti-diabetic effects of numerous TCM interventions have been confirmed, few studies have focused on related high-quality clinical evidence in elderly people.Zhang and her colleague conducted the only meta-analysis to survey the evidence on TCM and natural products for blood glucose control in elderly patients with diabetes, providing new insights for future clinical practice [40].

Multiple Complicated Diseases Make Medication Management More Complex for Elderly Patients with Diabetes
Elderly patients often have complex underlying medical conditions.Polymedication is common and difficult to avoid in elderly patients with diabetes, making matters worse [116].Decreased liver and kidney function in elderly individuals, coupled with the use of multiple medications, increases the risk of drug interactions and adverse reactions [117].To mitigate these risks, it is imperative for elderly individuals to adhere to safe, rational, and standardized medication practices, following their healthcare provider's guidance for precise drug use.Dosage adjustments should be tailored to the individual [9,118].It is imperative for family members to assist in enhancing medication adherence, by ensuring that medications are taken at the prescribed dosage and on schedule [119].The management of multiple medications can be intricate, particularly for patients with poor compliance and cognitive decline.Elderly patients with diabetes mellitus frequently suffer from comorbidities necessitating multiple therapeutic interventions, underscoring the importance of vigilance and comprehension regarding drug interactions and effects, to mitigate the risk of inappropriate medication use.Due to its multitarget properties, TCM and natural products have demonstrated efficacy in treating a range of concurrent conditions, such as geriatric cardiometabolic and systemic metabolic disorders [120,121].

Elderly Patients with Diabetes Combined with Cardiovascular Disease (CVD)
Diabetes mellitus is a significant comorbid condition associated with CVD and is the primary cause of morbidity and mortality in individuals with T2DM [122,123].Individuals with diabetes have a 2-3 times greater risk of developing CVD than those without diabetes [124].Diabetes also serves as a notable risk factor for heart failure (HF), with a 22.3% greater prevalence of HF and a 56% greater prevalence of hospitalization in elderly diabetes patients [125,126].Furthermore, older individuals with diabetes have a 10-fold greater risk of mortality from HF than those without diabetes [127].In addition, for every 1% increase in glycosylated hemoglobin, the risk of heart failure increases by 8~36%, and the risk of HF in diabetic patients increases with age, coronary heart disease, and peripheral vascular disease [128].TCM and natural products have been utilized in a series of beneficial attempts in this regard, and the related evidence is summarized in Table 6.Abbreviations: CHD = coronary heart disease; DM = diabetes mellitus; ECG = electrocardiograph; LDL-c = lowdensity lipoprotein cholesterol.

Elderly Patients with Diabetes Combined with Metabolic Syndrome (MS)
The prevalence of MS differed by 48.91%, according to the International Diabetes Federation criteria, and 46.80%, according to the ATP III criteria [135].The elevated prevalence of metabolic syndrome among elderly individuals with diabetes mellitus, particularly in older females, may be attributed to alterations in hormone levels post-menopause and diminished metabolic function [136,137].Tailored treatment for hypertension is recommended for the majority of elderly diabetic patients, with a focus on individualized target levels [138].In elderly patients with diabetes and hypertension, despite being at increased risk, the blood pressure management goal can be adjusted to 140/90 mmHg [9,139].Given the significant variability in blood pressure, ambulatory blood pressure monitoring is recommended.The prevention of hypoglycemia and hypotension, along with the associated complications, should be prioritized when managing diabetes and hypertension in the elderly population.Research indicates that lipid-lowering therapy may decrease cardiovascular risk among older individuals.It is imperative to consider the balance between the benefits and risks, potential drug interactions, adverse effects, and individual preferences for lipid-lowering agents [140,141].This decision should be informed by a thorough evaluation of factors such as life expectancy, frailty, comorbidities, liver and kidney function, and economic considerations.
TCM and natural products can reduce a patient's weight, lower their blood pressure, and lower their lipids.There is some evidence from basic research and small sample clinical studies to verify the therapeutic effect of TCM and natural products on metabolic syndrome.However, only one single clinical systematic review was identified on TCM and natural products for diabetes in conjunction with metabolic syndrome, specifically examining the effects of Crocus Sativus L. on metabolic profiles in patients with diabetes mellitus or metabolic syndrome [142].The effectiveness and safety of treatments for diabetes and metabolic syndrome are still uncertain due to the limited quality and heterogeneity of the existing studies on the topic.

TCM and Natural Products Have Advantages in Terms of the Management of Common Symptoms in Elderly Patients with Diabetes
The efficacy of TCM and natural products in managing complex symptoms is a notable feature over that of Western medicine [143,144].However, the existing evidence supporting the use of TCM and natural products for common symptoms, such as urinary incontinence, dizziness, falls, constipation, and frailty, is lacking, and related research and clinical practices are mostly based on empirical treatment.There is a dearth of systematic reviews and meta-analyses on the application of TCM and natural products for these symptoms in elderly individuals with diabetes.However, we did not search for any registered trials on common symptoms in elderly patients with diabetes.More clinical trials need to be conducted to demonstrate the potential benefits of TCM and natural products in this population.It is evident that TCM offers advantages in managing multiple symptoms, including those that may not be effectively addressed by Western medicine.Throughout the treatment regimen, TCM practitioners tailor comprehensive interventions to the individual patient's constitution and symptoms, aiming to restore the balance of Yin and Yang, enhance the circulation of Qi and blood, and effectively manage diabetes.Additionally, dietary control, physical activity, and regular monitoring of blood glucose levels are crucial components of diabetes management for individuals receiving TCM and natural product treatments [145,146].

TCM Offers a Complementary Solution to the Management of Diabetes in Elderly People and Common Diabetic Complications in Elderly People
The existing therapeutic approaches for managing refractory complications in diabetes patients are limited.Li et al. [147] conducted a comprehensive review of the cardiovascular, renal, and retinal outcomes associated with various anti-diabetic interventions in individuals with diabetes mellitus.The interplay of individual patient characteristics frequently plays a crucial role in influencing the adherence and adjustment of chronic kidney disease patients to the ramifications of heightened medication regimens.These factors frequently pose challenges in medical management, resulting in diminished renal function and general debility [148].Additionally, diabetic panvascular diseases, including diabetic retinopathy (DR), diabetic cardiomyopathy (DC), diabetes-related coronary heart disease (CHD), and diabetic peripheral neuropathy (DPN), present as troublesome complications.Pioneering TCM research has been conducted to address these complications, and we provide a review of the related evidence in Table 7.

Challenges and Future Perspectives
The favorable acceptance rate of TCM and natural products among the elderly population in China underscores the imperative for the establishment and dissemination of population-specific prevention strategies.Ethnopharmacology-focused research endeavors not only offer a scientific foundation for determining optimal dosages and potential toxicological impacts within local communities, but also hold promise for the development of more efficacious multitarget pharmaceuticals aimed at preventing and treating a range of ailments, including diabetes, in elderly people.Learning from the successful research experience involving Artemisinin, a selection of effective drug targets of TCM and natural products under the guidance of unique TCM theory accelerates the drug discovery process.TCM and natural products also play a role in enhancing the effectiveness of anti-diabetes medications and in the prevention and management of complications, offering a novel perspective.In the process of drug discovery, a crucial mechanism of diabetes provides directions for target selection.For example, the conceptualization of gluco-cardio-renal conditions helps to guide researchers to explore multitarget anti-diabetes medications, while that is exactly what TCM is good at.By integrating various disciplines, including epidemiology, clinical, and experimental monitoring, we conducted a comprehensive investigation and analysis of the clinical dilemmas in elderly diabetes (Figure 1).This study aims to establish a robust scientific foundation for clinical practice.Following a thorough examination of diabetes in the elderly population, specific intervention strategies are implemented, and their effectiveness in enhancing patients' quality of life and mitigating the occurrence of complications and mortality is assessed.

Challenges and Future Perspectives
The favorable acceptance rate of TCM and natural products among the elderly population in China underscores the imperative for the establishment and dissemination of population-specific prevention strategies.Ethnopharmacology-focused research endeavors not only offer a scientific foundation for determining optimal dosages and potential toxicological impacts within local communities, but also hold promise for the development of more efficacious multitarget pharmaceuticals aimed at preventing and treating a range of ailments, including diabetes, in elderly people.Learning from the successful research experience involving Artemisinin, a selection of effective drug targets of TCM and natural products under the guidance of unique TCM theory accelerates the drug discovery process.TCM and natural products also play a role in enhancing the effectiveness of anti-diabetes medications and in the prevention and management of complications, offering a novel perspective.In the process of drug discovery, a crucial mechanism of diabetes provides directions for target selection.For example, the conceptualization of gluco-cardio-renal conditions helps to guide researchers to explore multitarget anti-diabetes medications, while that is exactly what TCM is good at.By integrating various disciplines, including epidemiology, clinical, and experimental monitoring, we conducted a comprehensive investigation and analysis of the clinical dilemmas in elderly diabetes (Figure 1).This study aims to establish a robust scientific foundation for clinical practice.Following a thorough examination of diabetes in the elderly population, specific intervention strategies are implemented, and their effectiveness in enhancing patients' quality of life and mitigating the occurrence of complications and mortality is assessed.TCM and natural products have multiple pathways and multitarget metabolic regulatory properties.Highly potent chemical compounds used for elderly diabetes are summarized and their chemical structures are shown in Figure 2.Although numerous achievements have been made regarding TCM and natural products in regulating glucose and lipid metabolism, there still needs to be further in-depth research in this regard and there is still a long way to go for the application and translation of TCM and natural products into the clinical field.We have to admit that the biological characterization of TCM and natural products for elderly diabetes is at a very early stage, most of them are not fully characterized in vitro and in vivo.Also, the shortage of TCM and natural products in regard to various aspects such as low solubility, low bioavailability, and low tissue targeting, need to be overcome.The following suggestions are possible research directions with value based on TCM and natural products for treating disorders in elderly diabetes.ous natural products from plants or synthesis methods make the composition of TCM definite and clear.Moreover, there is a need to ascertain the applicability of current standards for assessing the clinical efficacy of modern medicine to TCM and natural products; (10) More comprehensive and high-quality verification experiments are needed to test the crucial effects of the hub genes selected in this study, to draw more precise and credible conclusions.

Conclusions
In comparison to younger individuals, elderly patients exhibit decreased tolerance to blood glucose exposure, diminished tissue and organ reserves, and elevated susceptibility to medication-related risks.TCM practices in China offer a novel perspective on this matter.Active natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery.This review highlights the significant therapeutic potential of TCM and natural products in managing diverse manifestations of diabetes in the elderly population.And there is a clear conclusion that TCM and natural products could: (1) improve the prevention of diabetes in elderly individuals, (2) maintain nutritional balance and sport health, (3) manage clinical symptoms, (4) control and even reverse diabetes and diabetic complications, and (5) provide a complementary and alternative therapy.As for the selection of the best treatment, a well-designed network meta-analysis may provide the final answer.Also, experimental studies are currently being conducted to investigate the efficacy of TCM and natural products in treating elderly patients with diabetes, with a focus on elucidating the underlying mechanisms involved.Future research efforts should prioritize the integration of high-quality clinical evidence and the exploration of novel pharmacological insights related to natural products for the management of diabetes in the elderly population.It is imperative to develop a comprehensive, integrative, and individualized treatment approach for elderly patients with diabetes, with the utilization of TCM and natural products playing a crucial role in optimizing clinical outcomes and maximizing therapeutic benefits.

Supplementary Materials:
The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ph17070953/s1,Additional File S1: Search strategy and selection criteria; Additional File S2: Table S1-S3.Table S1: Registered trials on TCM and natural products for primary prevention of diabetes; Table S2: Registered trials on TCM and natural products for diabetic cognitive decline; Table S3: Registered trials on TCM and natural products for diabetic sarcopenia, frailty, and obesity in the elderly.
Author Contributions: Conception and design: all authors.Provision of study materials or patients: C.X. and Y.C. Collection and assembly of data: all authors.Data analysis and interpretation: C.X., H.W., L.Z. and X.T. Manuscript writing: all authors.Final approval of manuscript: all authors.All authors are accountable for all aspects of the work.All authors have read and agreed to the published version of the manuscript.

Figure 1 .
Figure 1.Dilemma in elderly diabetes and the role of TCM and natural products in elderly diabetes.The person used to represent elderly diabetes in this figure is Fu Du, a prominent Chinese poet in the Tang dynasty, who is said to have suffered from diabetes near the end of his life.Yin (black background) and

Figure 1 .
Figure 1.Dilemma in elderly diabetes and the role of TCM and natural products in elderly diabetes.The person used to represent elderly diabetes in this figure is Fu Du, a prominent Chinese poet in the Tang dynasty, who is said to have suffered from diabetes near the end of his life.Yin (black background)

Figure 2 .
Figure 2. Example of TCM and highly potent chemical compounds used for elderly diabetes and their chemical structure.(1) The development of novel elderly diabetes patient-centered TCM and natural product treatments.Search for more effective TCM and natural products to enhance the therapeutic effect; (2) Transition from experience-based to evidence-based approaches in TCM and natural products.Facilitate the establishment of guidelines and promote international collaboration in addressing elderly diabetes patients; (3) Clinical trials: Carry out large-scale clinical trials to encompass a more representative population of cases and controls.Enhance the dependability and precision of research findings, as well as delving deeper into the variations in the effectiveness of antidiabetic medications; (4) Explore a wider range of study methodologies beyond relying solely on RCTs and case reports.Additional clinical evidence, such as real-world studies, may provide a more accurate representation of the clinical efficacy of TCM; (5) Employ novel evaluation standards tailored to the unique features of TCM.Investigate the correlation between TCM syndromes, treatment protocols, TCM applications for specific-patient populations, and utilize artificial intelligence in TCM practice; (6) Personalized treatment: A comprehensive examination of factors, including drug mechanisms of action, drug metabolism, and genetic polymorphisms.Elucidate the

Table 1 .
Evidence in systemic reviews and meta-analyses on TCM and natural products for the primary prevention of DM.

Table 2 .
Evidence in systemic reviews and meta-analyses on TCM and natural products for diabetic cognitive decline.

Table 3 .
Evidence in systemic reviews and meta-analyses on TCM and natural products for diabetic sarcopenia, frailty, and obesity in the elderly.
Reduced body weight, BMI, and waist circumference; reduced TC and LDL-c levels 33 2503
30CST = 30 s chair stand test; SST = sit-to-stand test; TUGT = timed up and go test; FOF = fear of falling; DBP = diastolic blood pressure; MMSE = Mini-Mental State Examination; QoL = quality of life.

Table 4 .
Evidence included in systemic reviews and meta-analyses on TCM exercise for diabetes and related complications in the elderly.

Table 5 .
Evidence included in systemic reviews and meta-analyses on TCM and natural products for blood glucose control in elderly diabetes.

Table 6 .
Evidence included in systemic reviews and meta-analyses on TCM and natural products for elderly diabetes combined with cardiovascular disease.

Table 7 .
Evidence in systemic reviews and meta-analyses on TCM and natural products for the management of common diabetic complications in elderly diabetes.